17-Phenyl-18,19,20-trinor-PGF2α and its derivatives of Formula [1b]:
wherein    the bond between carbon 1 and 2 is either a single bond (C1—C2) or a double bond (C1═C2), and R6 is selected from the group consisting of alkoxy and alkylamino, are synthetic structural analogs of prostaglandins with ocular hypotensive activity (B. Resul et al., J. Med. Chem., 1993, 36, 243 and U.S. Pat. No. 5,688,819). 17-Phenyl-18,19,20-trinor-PGF2α N-ethylamide (Bimatoprost) (New Drug Application (NDA) 21-275 published by the FDA) and 13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2α isopropyl ester (Latanoprost) (The Merck Index, 12th Ed., 5787) are believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routs. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.
The known methods for the synthesis of compounds of formula [1b] (see U.S. Pat. Nos. 3,931,279; 5,223,537; 5,698,733; and 5,688,819; WO95/26729, Prostaglandins, v. 9, 5 1975, J. Med. Chem., 1993, 36, 243) are shown in Scheme 1 below and include the stages of reducing the carbonyl group of compound [4] to yield a mixture of compounds [5] and [6a], separating the by-product [6a] from the desired compound [5] (C1═C2 and R2=H) by column chromatography, and reducing the compound [5] (C1═C2 and R2=H) (optionally, after OH-deprotecting/protecting procedures and/or C1═C2 double bond catalytic hydrogenation) with diisobutylaluminum hydride at temperature −70 to −80° C. to give compound [11], reacting the compound [11] with a metal salt of 5-(triphenylphosphoranylidene)pentanoic acid to obtain compound [1a] which yield (optionally after deprotecting the hydroxyl groups) compound [1b]:

However, this method is problematic since (a) the by-product [6a] is not regenerated; (b) it is difficult to separate the by-product [6a] from the desired compound [5] (C1═C2 and R2=H) and (c) it is difficult to scale-up the highly exothermic reduction of [5] (C1═C2 and R2=H) with DIBAL-H at such low temperature conditions.